Amyloid-beta (Aβ) cleaved from amyloid precursor protein (APP) has been proposed to play a central and causative role in the aetiology of Alzheimer’s disease (AD). APPswe/PSEN1dE9 (APP/PS1) transgenic mice display chronic Aβ accumulation and deposition in the brain. L-arginine is a semi-essential amino acid with a number of bioactive metabolites, and altered arginine metabolism has been implicated in the pathogenesis and/or the development of AD. This study systematically investigated how arginine metabolic profiles changed in the frontal cortex, hippocampus, parahippocampal region and cerebellum of male APP/PS1 mice at 4, 9 and 17 months of age relative to their sex- and age-matched wildtype controls. Immunohistochemistry demonstrated age-related Aβ deposition in the brain. High-performance liquid chromatography and mass spectrometry revealed age-related increases in glutamine, spermidine and spermine in APP/PS1 mice in a region-specific manner. Notably, genotype-related increases in spermine were found in the frontal cortex at the 9-month age point and in the frontal cortex, hippocampus and parahippocampal region at 17 months of age. Given the existing literature indicating the role of polyamines (spermine in particular) in modulating the aggregation and toxicity of Aβ oligomers, increased spermidine and spermine levels in APP/PS1 mice may be a neuroprotective mechanism to combat Aβ toxicity. Future research is required to better understand the functional significance of these changes.Because obsessive-compulsive disorder (OCD) is a highly impairing and often chronic psychiatric disorder, there is high interest in novel add-on or alternative intervention approaches. The error-related negativity (ERN), a response-related ERP occurring shortly after incorrect responses, might provide a promising target for novel interventions. Increases in the ERN have been reliably shown in OCD and are viewed as an important biomarker for the disorder. The ERN has been functionally associated with a heightened response to errors as negative, potentially harmful events. Attention Bias Modification (ABM) may be one promising strategy to reduce the ERN. Thus, in the current study, we used ABM training with the aim to reduce the threat value of errors and thus the ERN in OCD. Participants with OCD (n = 23) and healthy participants (n = 24) performed a 20-minute probe detection task in a condition that trained to attend to neutral and away from negative stimuli, while another group of healthy participants (n = 24) performed a sham version of the training. Results indicated a significant reduction of initially increased ERN amplitudes in the OCD group after the training, whereas in both healthy subgroups no significant changes in ERN were observed, resulting in non-significant group differences after ABM. These results indicate that ABM training may be a viable intervention to reduce ERN in participants with increased error-signaling, as in OCD. The current study serves as a clinical pilot investigation for future studies needed to elucidate underlying mechanisms, clinical effects and long-term outcome.Cardiac vagal control (CVC), as indexed by abnormalities in resting, reactivity, and recovery levels of respiratory sinus arrythmia (RSA), has been proposed as an index of impaired self-regulatory capacity in depression. Aerobic exercise has been shown to improve positive and negative affective responses and influence autonomic function; however, it is unknown whether exercise impacts RSA reactivity and subsequent recovery to emotional challenges among individuals at risk for depression. The present study aimed to determine the effects of moderate-intensity aerobic exercise on RSA reactivity and recovery to a sad film. GSK2606414 research buy Using a within-subjects design, 47 individuals with variable symptoms of depression completed a 30-min session of exercise and a sedentary control condition on separate days prior to viewing a sad film. On the control day, individuals with elevated depressive symptom severity displayed less vagal withdrawal to the sad film and exhibited impaired post-film RSA recovery. Following exercise, individuals with elevated depressive symptom severity demonstrated a higher degree of vagal withdrawal to the sad film and subsequent post-film recovery that matched individuals with lower depressive symptom severity. These findings suggest that a single session aerobic exercise may be an effective approach to increase emotional and self-regulatory capacity among individual at risk for, or currently experiencing, depression.The school-age years is a period of increasing social interaction with peers and development of emotion regulation in facilitating that interaction. This study was an investigation of the neural correlates of emotional reactivity and reappraisal in typically developing school-age children elicited by threatening facial expressions of same-aged peers. This experimental paradigm is novel in eliciting event-related brain potentials (ERPs) to social stimuli that are ecologically valid to the everyday life of children. ERPs of 5- to 8-year-old children (N = 41, 18 females) were elicited by threatening (i.e., angry and fearful) and neutral child facial expressions, which were preceded by audio contextual cues. Three conditions differed in audio-image pairing neutral context-neutral expression (neutral condition), negative context-threatening expression (threat condition), and reappraisal context-threatening expression (reappraisal condition). In addition, parental reporting of childhood temperament was collected to determine if elicited ERP morphologies were associated with temperamental dimensions of negative affect, extraversion, and effortful control. Elicitation of the P100 and N170 did not largely differ between conditions; however, amplitude of the late positive potential (LPP), a marker of heightened emotional reactivity and attention, was greater for threatening faces relative to neutral faces. During the reappraisal condition, no differences in ERP activity was observed compared to the threat condition. Neural substrates of emotional reactivity to social threat from peers were evident; however, the lack of ERP modulation facilitating reappraisal and the lack of strong associations between ERP morphology and temperamental dimensions is indicative of heterogeneity in LPP elicitation underlying emotion regulation in children.